To advance the reliability of detecting tumor responses during anti-cancer therapy, this project will evaluate a dual sodium/proton biomarker. The central hypothesis to be tested purports that during efficacious anticancer therapy there is a correlation between Na MRI and proton diffusion (ADC) of tumors whereby both methods predict outcome before visible tumor shrinkage and, conversely, these responses differ in nonresponding tumors or during ineffective therapy. Joining ADC, an indicator of tumor cellularity, and sodium MRI provides an opportunity to evaluate tumor therapy by two pertinent physiological dimensions of cancer cells simultaneously. The results are essential for assessing therapeutic efficacy and, consequently, the enhanced care of cancer patients. Pixel by pixel sodium/ADC 2D analysis of the whole brain will provide a quantitative map of heterogeneous responsiveness of a tumor to therapy. The TSC changes in a rat glioma model can take place one week before any noticeable tumor shrinkage, thus sodium MRI has a predictive power for assessing tumor treatment outcome which will be investigated. In this project, the relationship of proton ADC and 3D Na MRI will be performed for a 9L rat brain tumor at a high magnetic field of 9.4 T during several chemotherapies. The second goal of this project is to evaluate tumor therapy by ADC together with changes in a specific pool of total sodium determined by Na binding, mainly to proteins. Chemotherapeutic brain tumor cell destruction decreases the amount of bound Na which is detectable by triple quantum Na signals (TQ). Changes of TQ Na signal are usually in the opposite direction to changes of SQ Na signals. This feature is expected to complement ADC analysis in differentiating between an edematous cell response and efficacious tumor therapy. Assessment of tumor therapy will be performed by novel sodium TQ signal detection. Innovations comprise a capability for optimal detection of a wide range of Na bindings, overcoming the main disadvantages of TQ methods troubled by low detection efficiency and the presence of multiple artifacts. In summary, broad assessment of advanced ADC biomarker of tumor cellularity, now in clinical testing, will be performed using sodium MRI. Additionally, imaging of bound sodium is included to facilitate the differentiation of edema from cell disintegration during tumor therapy. Sodium MRI applied to oncology will be evaluated for future translation to high field clinical MR scanners.